Search

Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29-14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate

Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29-14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate

Tidal boundaries are deemed to be the position of Mean High Water Spring (MHWS) Tide on the ground. This is subject to interpretation of available data, the interpretation of one person could vary to that of another and as a result the boundary in question could have different locations. This has been the subject of contention resulting in a stay on surveys placed on lots with tidal boundaries for three years by the Department of Natural Resources, Mines and Water (DNRMW). This allows time to investigate and find solutions to the issues associated with tidal boundaries. This project investigates the effect of tidal boundaries of wide shallow bays in general and Cleveland Bay in Townsville in particular. The objectives are: • To find a correlation between tidal levels and boundaries • To find the differences between the cadastral boundary location using traditional methods and where it is actually located • To find the relationship between tide levels at the principal tide gauge and other locations • To investigate the relationship between tide levels and ecosystem boundaries. This will be achieved by identifying suitable locations as test sites. The test sites will be used to monitor tide levels and the adjacent area surveyed topographically. The topographical survey will identify ecosystem boundaries and the position of MHWS. These boundaries will then be compared to the cadastral boundaries.

This title contains one or more publications.

A quantum wave packet calculation for the activated dissociative adsorption of H2 is presented. Restricting the motion of the molecule to lie within a plane normal to the surface we have treated all four molecular degrees of freedom exactly. We compare results obtained using two-, three-, and four-dimensional simulations on the same potential and show that by restricting the molecular orientation, important dynamical effects are lost. The potential employed in the calculations has been obtained using the effective medium approximation. In the simulations it has been possible to treat dissociation, rotations and diffraction on an equal footing. By including a rotational degree of freedom, it is seen that strong orientational effects occur near to the transition state and result in an anisotropic selectivity in the dissociation. By examining the state-to-state scattering probabilities, it is possible to use the nonreacting (scattered) fraction to provide information on the reactive potential energy surface. The Journal of Chemical Physics is copyrighted by The American Institute of Physics.